Temperature gradient capillary electrophoresis (TGCE) using the SpectuMedix Reveal-2410 Mutation Discovery System will accelerate identification of the DNA sequence underlying biological phenotypes and developmental processes. By combining temperature gradient electrophoresis with capillary electrophoresis it is possible to rapidly identify DNA fragments with mismatches in nucleotide sequence based on the melting temperature. By running sufficiently broad temperature gradients, mismatches in multiple fragments differing in size and nucleic acid sequence can be detected at efficiencies above 95% in a single run. This is a major advantage over other approaches to identify functional nucleotide sequence changes. Rather than sequencing an entire candidate gene, the Mutation Discovery System prioritizes the exon or region of DNA with mismatch between mutant and wild-type for nucleotide sequencing. The Reveal-2410 can then be used as a standard nucleotide sequencer to identify the nucleotide changes. Increased nucleotide sequencing is also needed due to expanded use of phage-based E. coli homologous recombination for rapid modification of large segments of genomic DNA for generation of constructs for knockout and transgenic mice. The instrument requested will benefit NIH funded research programs in the genetic control of rnyelination by Schwann cells, in the functional genomics of susceptibility to prion diseases, in the role of molecular motors in hearing, and in the developmental biology of the auditory system and congenital deafness. In addition to the demonstrated ability of this technology to reveal single base changes in fragments between 200 to 500 bp, such as isogenic mutations induced by ENU, novel uses, such ranking candidate genes underlying QTL, are likely to prove fruitful. The Spectrumedix Reveal 2410 will not only accelerate current research at McLaughlin Research Institute, but help in recruiting new biomedical researchers in the field of neurogenetics.